Inhibition of tumor angiogenesis (the growth of blood vessels towards the tumor mass) is a new, promising approach to the anti-cancer therapy. Inhibitors of angiogenesis such as angiostatin purified from urine of tumor- bearing mice have a potent antineoplastic activity in rodents. Therefore, we propose that angiogenesis inhibitors purified from urine of cancer patients could have a potent antineoplastic activity in humans. The goal of this project is to isolate new angiogenesis inhibitor (SBD 1) directly from urine of patients with bladder carcinoma. Our preliminary results show that partially purified urine from patients with bladder carcinoma inhibits selectively the growth of endothelial cells. Moreover, the chromatographic and filtration profiles of this inhibitory activity, protease sensitivity as well as antibody testing indicate that most likely it belongs to a novel anti-angiogenic protein. Using several combinations of chromatographic techniques, we intend to rapidly isolate this inhibitor. Furthermore, we will test it for the potential anti-tumoral activity in mice, and determine its amino acid sequence. This project will therefore result in the isolation of a new angiogenesis inhibitor with potential anti-tumor activity, which can have a tremendous commercial importance both as a laboratory research reagent and as a clinical drug. PROPOSED COMMERCIAL APPLICATIONS: The need for new, better anticancer medicines is immense. Moreover, an angiogenesis inhibitor like ours could be used for the treatment of certain cardiovascular diseases and macular degeneration. Therefore, there is a large, multibillion dollar market for the type of molecule(s) that we propose to purify. We strongly believe that a novel efficient angiogenesis inhibitor like ours will attract joint venture partners and will be taken to clinical trials. Meanwhile, it can be commercialized as a reagent for laboratory research on angiogenesis.